No Evidence of Transdifferentiation of Human Endothelial Progenitor Cells Into Cardiomyocytes After Coculture With Neonatal Rat Cardiomyocytes

Abstract

Background-Recent studies have suggested the differentiation of human endothelial progenitor cells (huEPCs) isolated from peripheral blood into cardiomyocytes. This study investigates whether, when cocultured, neonatal rat cardiomyocytes (NRCMs) can induce transdifferentiation of huEPCs into cardiomyocytes. Methods and Results-Coculture experiments with 1,1Ј-dioctadecyl-3,3,3Ј,3Ј-tetramethylindocarbocyanine (DiI)-labeled huEPCs and NRCMs have been performed. Cocultures have been analyzed by means of flow cytometry, 3D confocal laser microscopy, species-specific reverse transcriptase-polymerase chain reaction for the expression of human cardiac marker genes, and electron microscopy. Although fluorescence-activated cell sorting (FACS) analysis and conventional wide-field fluorescence microscopy suggested the existence of DiI pos cardiomyocytes in cocultures, no convincing evidence of cardiac differentiation of huEPCs has been obtained. Apparently, DiI pos cardiomyocytes were identified as necrotic NRCMs or NRCM-derived vesicles with high levels of autofluorescence or, alternatively, as NRCMs lying on top of or below labeled huEPCs or huEPC fragments. Accordingly, no expression of human Nkx2.5, GATA-4, or cardiac troponin I was detected. Conclusions-No

Concise Review: Cell Therapy and Tissue Engineering for Cardiovascular Disease

“…The significant therapeutic effects by the transplantation of autologous skeletal myoblast sheets were also confirmed in large-animal modes (a pacing-induced canine dilated cardiomyopathy heart failure model and a porcine ischemic myocardium model) [72,73]. The transplantations of several adult stem cell sheets (adipose-derived and menstrual blood-derived mesenchymal stem cell sheets, and CSC sheets) also gave favorable therapeutic effects in small-animal models [41,74,75]. Several trials to enhance the therapeutic effects were performed.…”

“…Although EPCs are the progenitors of endothelial cells, human EPCs can also be differentiated into cardiomyocytes by coculturing with rat cardiomyocytes, although the efficiency was very low (0.4 Ϯ 0.03%) [39,40]. On the other hand, another group was unable to confirm the differentiation of EPCs into cardiomyocytes [41]. Bone marrow cells also contain mesenchymal stem cells (MSCs), which have a multipotency including cardiac differentiation [15].…”

Regenerative Potential of Intravenous Infusion with Mononuclear Cells in Cord Blood and G-CSF-Mobilized Peripheral Blood

“…The effects of MSCs and MNCs have been compared in various experimental settings ( [19][20][21]. The end results of these effects are the replacement of lost myocardial tissue and rescue of ischemic and hibernating tissue, and improvement of left ventricular function.…”

Perspectives on Stem Cell Therapy for Cardiac Regeneration

“…Various studies involving the administration of EPCs have shown positive effects on improving damaged heart function, 38,39 but the EPCs did not differentiate into cardiomyocytes after transplantation. 40 However, it was evident that administering EPCs resulted in improved cardiac function. Such an improvement in cardiac function was probably related to the role of EPCs in promoting angiogenesis and supplying sufficient nutrients and oxygen for the survival and division of host cardiomyocytes, as well as replacing novel cardiomyocytes with endogenous stem cells, and also by exerting an additional positive effect on the survival of the replaced cardiomyocytes through a paracrine effect.…”